The goal is to gain further insight into mechanisms governing T cell activation and its regulation. To this end, a large panel of L3T4+ inducer T cell clones has been generated. These clones display distinct differences in their requirements for activation. For example, some clones respond to antigen presented either by macrophages or B cells, while others respond to antigen presented by macrophages but not by B cells. Some clones respond to determinants present on B cells but not macrophages. Several of the nominal antigen specific T cell clones are also reactive against allogeneic MHC and Mls determinants. Using these clones I propose to: 1) examine T cell clones which fail to proliferate in response to antigen presented by B cells in order to determine a) how their activation requirements differ from those of T cell clones which do respond to antigen presented by B cells and b) how these two types of clones differ in their ability to induce antibody synthesis; 2) examine in detail the activation of T cell clones by Mls determinants and attempt to characterize these determinants; 3) examine mechanisms regulating the activation of NP-specific inducer T cells by analyzing their inhibition by NP-specific suppressor factors derived from NP-specific suppressor T cell hybridomas. This proposal will attempt to increase our understanding of the molecular and cellular interactions governing T cell activation and its suppression. Such an understanding is vital to the favorable manipulation of the immune system in many disease states.